Certain substituted 2,6-diamino-4-methyl-nicotinonitriles the corresponding nicotinamides and derivatives thereof

ABSTRACT

2,3,6- AND PREFERABLY ALSO 4-SUBSTITUTED PYRIDINE DERIVATIVES BEARING THE RADICAL OF AMMONIA OR A PRIMARY AMINE IN THE 2- AND 6-POSITIONS. The compounds are eminently suitable as coupling components for the production of azo dyes, the coupling taking place in the 5-position.

United States Patent [191 Lamm et al.

[ CERTAIN SUBSTITUTED 2,6-DIAMINO-4-METHYL- NICOTINONITRILES THE CORRESPONDING NICOTINAMIDES AND DERIVATIVES THEREOF [75] Inventors: Gunther Lamm; Johannes Dehnert,

both of Ludwigshafen, Germany [73] Assignee: Badische Anilin & Soda-Fabrik Aktiengesellschaft, Ludwigshafen, Rhine, Germany [22] Filed: Jan. 31, 1973 [21] Appl. No.: 328,459

[52] U.S. Cl 260/294.9, 260/156, 260/295.5 A, 260/2955 B, 260/2955 T [51] Int. Cl C07d 31/46 [58] Field of Search... 260/294.9, 295.5 A, 295.5 B, 260/2955 T [56] References Cited UNITED STATES PATENTS 3,433,795 3/1969 Hyden et a1 260/2955 T Dec. 10, 1974 3,664,996 5/1972 Bertie et al. 260/2955 A OTHER PUBLICATIONS Karrer, Organic Chemistry, 4th English Edition, Page 928, Elsevier Pub. Co., (NY), 1950.

Chemical and Engineering News, page 18, Apr. 3, 1972.

Primary Examiner-Alan L. Rotman Attorney, Agent, or FirmJohnston, Keil Thompson & Shurtleff 5 7] ABSTRACT 6 Claims, N0 Drawings 1 2 CERTAIN SUBSTITUTED 2 )2 2 )z 2)3 2 )q 2 )a 2- 2,6-DIAMlN-4-METHYL-NICOTINONITRILES 4 7 2 )3 2 4 3 2 )3 2 4 2 5 THE CORRESPONDING NICOTINAMIDES AND (CH2 )3 2 4 3 )2 2 )3 2 4 4 9v DERIVATIVES THEREOF 2 )3 2 4 2 6 5, 2)3 2 4 2 4 s 5 This invention relates to compounds of the formula: 5

t noao zmocfias l0 2 MN HN -z moou-clnoom. (01mmolwln cmt.

l lllu (illll where R is hydrogen, alkyl of one to seven carbon atoms or phenyl, the radicals Z independently of one t:mount u oout. (onmofiuiumoouu, other mean hydrogen or an unsubstituted or substi- C111 CH3 tuted'aliphatic, cycloaliphatic, araliphatic or aromatic radical and corresponding radicals in which the groupings X is cyano or carbamoyl. More particularly, the invention relates to com- -OC,H,,-,()C}I--CH3- or ocmcupounds of the formula (la): Cm CH are present twice, three .times or four times, CH Cl-l OCH CH CH OC H CH Cl-i OC l-l I cn cn ocnr cn cu oc n (cuo ocn (In) zh z s z)3 3 1 2)3 4 9, in which R is hydrogen, alkyl of one to seven carbon atoms or (CHQQOOHZCFHCHM H pheny] O2H5 X is carbamoyl or cyano and the radicals R independently of one another are unsubstituted or (CI-I OCH C H (CH 0C2 4 6 5, z)a s s substituted aliphatic, cycloaliphatic, araliphatic or aromatic radicals and one of the radicals R may be 7 t v V hydrogen and at least one of the radicals R contains mimcmo LIHUM) (FHCHZO Cans an oxygen atom. CH3

Examples of alkyl radicals R are ethyl, n-propyl, isoonornoc moms, J, Q Z h, propyl, butyl, pentyl, a-ethylpentyl and preferably on 0113 011i y I OH CI-IOC l'In, CIIQCI[OC2H4COI15, CHgCIIOCuH;-,

Examples of radlcals Z or R are alkyl of one to eight I l CH3 ona on;

carbon atoms which may be interrupted by oxyten atoms and which may bear hydroxy, alkoxy, cyano, cy- (OHZMOCGHH H (OHMCN: cloalkoxy, aralkoxy or aroxy as substituents, cycloalkyl and polycycloalkyl which may bear hydroxy, chloro, (011:!)5CN, (ClI2)uCN, 0112mm mon-moolnn hydroxyalkyl, chloroalkyl or alkyl as substituents, aralkyl of seven to fifteen carbon atoms, phenyl which may bear chloro, hydroxy, alkoxy, alkyl, hydroxyalkoxy or hyroxyalkyl as substituents, or alkenyl, pyrrolidonylaland C l-l CI-l instead of C l-l 2. unsubstituted or substituted cycloalkyl or polycykyl or carboxyalkyl. 5O cloalkylz Examples of individual radicals Z or R are: K 1. unsubstituted or substituted alkyl: H H H I; II

V V on, omorr, ol-nci, CH CH OH, (CH OH,

omonon, CH-CH OH, M (2m I oinoinou, l 2)4 QG 3. aralkyl:

and C l-I CH instead of C H 4. unsubstituted or substituted phenyl:

l (CH2),.N

in which n is 2,3, 4 or 6.

For the production of compounds of formula (I), compounds of formula (ll):

in which Y is chloro or a radical of the formula NHR, and X, R and R have the meanings given above may be reacted with an amine of the formula:

Reaction conditions which affect the exchange of the chlorine atom(s) include the temperature, the amine component, the molar ratio of the reactants and any diluent or solvent or acid-binding agent used. Amines of low boiling point may of course be reacted under superatmospheric pressure. The reaction with the amine is conveniently carried out at elevated temperature, a temperature of from about 0 to l 10C being adequate for the exchange of the first chlorine atom depending on the basicity of the amine, while temperatures in the range from about 60 to 180C being advantageous for exchange of the second chlorine atom.

Amines of high basicity react more rapidly than those of low basicity; when exchanging the second chlorine The presence of water does not cause any disturbance.

The addition of acid-binding agents is advantageous because then the total amount of amine to be reacted is available for the exchange. Substances which do not 5 themselves react with the chloropyridine derivatives are suitable as acid-binding agents; for example tertiary amines such as triethylamine, tributylamine, triethanolamine, ethyldiisopropylamine, caustic soda solution, sodium carbonate, magnesium oxide or calcium carbonate are suitable. in the case of inexpensive amines, an excess of the amine to be reacted may also serve as acid-binding agent.

Compounds of the formula (lb):

m CN RI1N\\N NflR a in which R has the meanings given above are of particular industrial significance.

Examples of preferred radicals R containing oxygen are:

CH CH OH, CH CH CH Ol-l,

(JllgCllOll, (Ill-(311 011,

CH3 CH3 3U CH3 CH CHa CH; O H

atom it is advantageous to use an excess of amine I (more than 10 percent), whereas the first chlorine atom reacts immediately with a molar amount of amine. Examples of suitable diluents or solvents which may be added are alcohols such as methanol, ethanol or isopropanol, glycols and glycol ethers such as methyl glycol, ethyl glycol or butyl glycol, hydrocarbons and halohydrocarbons such as benzene, toluene, ethylene chloride, chloroform, trichloroethylene or clilorobenzene, and also acetone, tetrahydrofuran, dimethylformamide, N-methylpyrrolidone or dimethylsulphoxide.

CIlu

(Cl-I930 CH CHaO Cl [a Examples of preferred oxygen-free radicals which are preferably used in combination with an oxygencontaining radical R are besides H:

l 1 Hz sHs. C2H. 6H5. aucus.

.Parts and percentages referred to are by weight unless otherwise stated.

EXAMPLE 1 187 parts of 2,6-dichloro 3-cyano-4-methylpyridine is suspended in 500 parts by volume of methanol. 80 parts of 2-hydroxyethylamine is then added at 40 to 45C followed by 100 parts of triethylamine. The mixture is stirred for five to six hours at 45 to 50C, about 250 parts by volume of methanol is distilled off and the residue is diluted with 1000 parts by volume of water. After acidification with 50 parts of concentrated hydrochloric acid, the whole is stirred for 1 hour, the deposited precipitate is filtered off, washed with water until neutral and dried. About 210 parts of a colorless powder of the formula:

is obtained. The powder contains a minor amount of a product of the formula:

The mixture melts at 115 to 120C.

125 parts of this powder is stirred with 300 parts by volume of methoxyethylamine for six hours under reflux.

Excess methoxyethylamine is then extensively distilled off so that the temperature may rise to 130C and the whole is then diluted with 500 parts of water. The mixture is stirred for one hour at 0 to 10C and the deposited precipitate is filtered off, washed with water and dried. The main product has the formula:

(lll

and there is a minor amount of a product having the formula:

The product is colorless and melts at to 78C.

EXAMPLE 2 A suspension of 50 parts by volume of methanol, 22 parts of norbornylamine, 37 parts of 2,6-dichloro-3- cyano-4-methylpyridine and 25 parts of triethylamine is stirred for six hours at 40 to 50C. Then about 200 parts by volume of ice-water is added, the whole aciditied to pH 1, and the precipitated product of the formula CH3 (ION (1- N1I@ (which still contains a small proportion of 2-chloro-3- cyano-4-methyl-6-norbornylaminopyridine isomers) is filtered off, washed with water and dried. About 45 parts of a colorless powder is obtained which melts at to 112C.

45 parts of the moist powder is heated at C to C with 50 parts of the amine of the formula:

the water being allowed to evaporate. After stirring for 5 hours at 130 to 140C the reaction is completed. The whole is allowed to cool and is acidified with 130 parts by volume of acetic acid. A solution of the coupling component mixture of the formulae:

is obtained, the amount of the product of formula (11) being small.

When the mixture thus obtained is coupled with pnitroaniline a dye is obtained which dissolves in dimethylformamide to give an orange solution.

EXAMPLE 3 A mixture of 300 parts by volume of N- methylpyrrolidone, 150 parts of 2,6-dichloro-3-cyano- 4-methylpyridine, 115 parts of p-anisidine and 90 parts of triethylamine is stirred for from six to 7 hours at 70C. it is then poured while stirring onto 1500 .parts of ice-water and acidified with hydrochloric acid to pH 1. About 220 parts of a colorless product of the formula:

is obtained which is isolated by filtration, washing with water and drying. The powder contains a minor amount of a product of the formula:

The mixture melts at 147 to 150C.

EXAMPLE 4 CONHz c1 JNHCH2 CHQ CHlOII The filtrate has caustic soda solution added to it until the pH is from to 6. A crystalline precipitate is thrown down which probably has the formula (II) @CONII:

This is filtered off, washed with water and dried. The product (11) thus obtained also contains traces of the product of the formula (I) and melts at 150 to 160C.

TAB L E 1 C O NH:

N NH-R Melting point, Number R C.

6 (CH2)30C91I5 7 C4H9 121-122 8 -C H13(11) 80-00 .l CHg(|3H-C1Tg -145 l0 s s 180490 OCH3 (C HzhOCHa 105 C3117 (1'1) 12-1 CH2CH2OH 130 (CH2CH20)'ZI{ 110 CH: CgI'Is 143 When 2,6-dichloro-3 -cyano-4-methylpyridine is treated by a method analogous to those described in Examples 1 to 3, there are obtained (by exchange of one chlorine atom) mixtures of 2-amino-3-cyano4- methyl-o-chloropyridine and 2-chloro-3-cyano-4- methyl-o-aminopyridine derivatives, the proportion of the Z-chloro-3-cyano-4-methyl-6-amino isomers being clearly less.

TABLE L! (llllz Melting point, Number R 18 (CII9)5COON11 85[)1 1) o }I[;I)5. 11;; 411 17 2. (CIIQCIIQODH 79-83 (0110 011113 00-100 1. (hllfln) 50430 23 031110) 952-105 2-i (Cl- 910C113 1585 25 1 V n CH $IIC4llo(n) (1) 02115 26 (0119 011 llU-11 t 27 1. (011211011 125 Ull:i

32 CH CH OIi 103-105 CII Cl'IaOlI 33 (|3l1(CH2)3C(CII T111 011:1 Oll IIQM l 30 ((Jll- 1);()-( lI;-(1r.ll:.

OCH;

4U CH 120-128 I CH3 1 Greasy product. 2 Tar becoming solid on prolonged standing. Viscous oil.

When the products set out in Tables 1 and 2 are treated with aliphatic or aromatic amines at temperatures above 100 or C respectively, the corresponding coupling products are obtained.

Shade after coupling with pared by always first introducing the radical R. parts of 26 diamino 3 cyano 4 methylpyridine is EXAMPLE 357 stirred with 200 parts by volume of concentrated sulphuric acid for ten hours at 50C. The whole is then allowed to cool, 250 parts of ice is added and it is left V is overnight. The deposited precipitate is filtered off and (3H3 washed witht acetone. After drying, 36 parts of a com lourless powder of the formula:

25 parts of the coupling component of the formula:

II-l\"CH -C]Ig-OC I E 6 v r CONHz S0429 is stirred with 75 parts of 90 percent sulphuric acid for six to eight hours at 80 to 100C. The reaction mixture 2 is then precipitated on 500 parts of ice, adjusted to pH 4 to 6 by adding caustic soda solution and extracted with ethyl acetate. After the extractant has been evapois obtained which melts at 250C with decomposition.

rated about 20 parts of the coupling component of the formula: I The free base of the formula:

ooNiu I f 0 is obtained as a dark oil. A red dye is obtained therefrom after coupling with diazotized p-nitroaniline is obtained from the salt by a conventional method.

TABLE (1 EXAMPLE 398 0111 190 parts of 2,6-dichloro-3-cyano-4-methylpyridine, I 750 parts of isopropanol and approx. 300 parts of am- CN 5 monia are stirred in an autoclave for 15 hours at 180C. H N R Nu m The mixture is allowed to cool, excess ammonia is N evaporated and 450 parts by volume of isopropanol is Melting distilled off. The residue is mixed with'approx. 600 Number R2 p parts of water, the pH is adjusted to approx. 0 with con- 42 115 CH5 12 13 10 centrated hydrochloric acid and the solution filtered. 178 Then 50 percent caustic soda solution is added until the 9 pH of the mixture is approx. 9, the mixture allowed to cool to O-l0C and then filtered, and the residue is ggjjjjjjj :gijiq g Iii washed with water and dried. 130 to 145 parts of a cola 3 l1 7 11 122-12 3&1 -o112 o11=- o11: oi12c11==o1n 77 15 (less powder of the formula 365 -C4Hn(l1) C4Hq(n) 97 366 CslI (ll) -C5H1:|(H) ()il CHa 307 1 .13 i

l[ II (;N

IIzN NrNIIz 369 175 ---Cl o1 is obtained which melts at 225C. s70 -o11-1c1115 cm-c1115 170 371 CHC1I?C1H5 -cHQo11,o11i,, 110

8 ii 8 ii 1205 1 5 an 115 374 8 4 (2) EXAMPLE 399 $2 $2 L 538 300 parts of 2,6-dichloro-3-cyano-4-methylpyridine CHZCHMHS 41 100 is mixed with about 500 parts by volume of liquid amsrs o112o11c1115 -o111o11c11I5 C11. 60 monia and treated in an autoclave for 2 hours at CH3 approx. 80C. Excess ammonia is allowed to evaporate, CH2 CHE CEH5 Cm 100, 1188 the residue IS diluted with approx. 2500 parts by volegu i mn) I}{I C 36 1 ume of water, and the pH is ad usted to 0 to l with hydrochloric acid. The insoluble residue is filtered off, 382 H washed with waterand dried. Approx. 260 parts of a 0m colorless powder of the formula ass --(:|1 -(:|1--o1115 #11 Tml I ll! i 384 ll (!ll N ()ll (lll- ()N 171F176 C 311.1 -(ll- -Cllg-(YN -o11Q-o11 -o111.-, (111.120 N 3116 "11 (o11? 5oN 142 Hydrochloride. C \N NH: 2 Tarry: becomes solid aft 01- prolonged standing.

TABLE 7 x l CONH: RZHN NHR* Shade when coupled with Example X R 387 (Illa ll ()I 2CII2()II Yellowish red. ass (:11. 11 01193011 Do.

389 om 11 (I]ICII-(J@U5 Do.

OII

(1112011410115 Do. QCII2()JI liluish red. (011; 3011 1)). o112 2o o112 2o11 Do.

cnmmonmou Do.

(lllzCligOll DU. (01191011 l)0. (011211011 Du.

31 32v which contains a minor amount of the isomeric 2- @113 UN chloro-3-cyano-4-methyl-6-aminopyridine and melts at 210C is obtained. -N1Ii 168 parts of this powder is mixed with about 170 parts of fi-hydroxyethylamine and 170 parts by volume 5 NH UL of isopropanol; The mixture is heated for 7 to 10 hours is obtained, a minor portion of which consists of 2- uncler reflux, the solvent is distilled off, the residue is amino-4-methyl-5-cyano-6-B- diluted with about 400 parts of water, and the pH is adhydroxyethylaminopyridine. justed to l to 2. A deep-colored solution of about 192 I 0 A greenish yellow dye may be obtained by coupling parts of the coupling component of the formula with diazotized Z-aminobenzonitrile.

TABLE 8 r l R NH N NH R Shade when coupled with CH; CN Golden yellow. 0 11:. CN Do. C3H7 CN D0. (EH CH3 (3N D0. CQHAOCIill CONH: Yellowish red. CaHaOCH: (:ONH: D0. (kl-C111 (IN Golden yello: C Hq(n) N Yellow orange. G l iam) CONll Yellowisli rod. GH CH=C1I= (-N Holden yellow.

ONII Ycllowish rod. (CH2)a 0 411 II (lflh (3N Omngo.

(HUG-1163(1) (CH 412 II (lllia (IONII: Red.

(]I'[((')I'I (|)(Gl.i:i)z

413 (3H3 UllaUHzOH CON: Red.

CH(C-H )a(|)(CH 414 (1)11 (UlIQnOll. (JUNlIg Red.

CI-1((JH;);({)(C1I;)2

415 CHgCI'IQOH (JONHQ Red.

(CH'QaN l 0 411' Q C H CH OH CQNH Red; (M.P. ISO-153 C.)

33 34 i' 3 CHzCHOH, cuc1n0u,

. compound of the formula l 5 (CH O(CH OH, --(CH O(CH OH.

mm NHZ -(CH ),OH, (CH OH, -(CH O(CH ),OH.

in which: CII(CIIii C\CHJl R is hydrogen, alkyl of one to seven carbon atoms or 10 (I)1r phenyl; J X is cyano or carbamoyl; and H 4), H .()(.lh(ll ;()|l. each Z, independently of one another, is hydrogen,

alkyl of one to eight carbon atoms, hydroxyalkyl of two to eight carbon atoms, cyanoalkyl of two to Cm u seven carbon atoms, alkoxyalkyl of two or three carbon atoms in the alkyl and one to eight carbon N H atoms in the alkoxy, cyclohexoxypropyl, benzylox- @011, @Cmon, mmnmr. ypropyl, B-phenyl-ethoxypropyl, phenoxypropyl, tolyloxypropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, hydroxycyclohexyl, B-hydroxyethoxycyclohexyl, norbornyl, hydroxynorbomyl, on, cmcu hydroxymethylnorbornyl, chloromethylnorbornyl, B-hydroxyethylnorbornyl, bicyclooctyl, phenylalkyl or tolylalkyl of one to four carbon atoms in the CH; CH:

alkyl, phenyl, phenyl substituted by methyl, methoxy, ethoxy, hydroxy, chloro or B-hydroxyethoxy, $H(CH')Q allyl, carboxyethyl, carboxypentyl, w-pyrrolidony- CHZOH lalkyl of two to six carbon atoms in the alkyl, June") Q -CH CH OCl-I -CH2CH2OC2H5, 43inccn,c1-10 can, (cn,),o(cn2)2on, (cH2 80(cH2)40H, (CH2. 45 AH, )a z)s (CH OC H OCH CH3 (CH OC H OC H JS (CH2)30 cncrnocrn z)a( .z 4)n n being 1, 2, 3 or 4, and and T being hydrogen, alkyl of one to four carbon atoms, 2 a 2 4 s 5;

benzyl, phenylethyl, cyclohexyl, phenyl or tolyl. and 2. A compound as claimed in claim 1 of the formula Z2 hydrogen an oxygencomammg mama] as fined for Z or an oxygen-free radical selected from CH3 the group consisting of Z is an oxygen-containing radical selected from the group consisting of CH CH OH, CH CH Ch Ol-i, -CH C H C H C H C H C H 3. The compound of the formula Illa N (Ill CH OClh l ON ilqlNHr 5. The compound of the formula 6. The compound of the formula NHCzIhCaIIs 

1. A COMPOUND OF THE FORMULA
 2. A compound as claimed in claim 1 of the formula
 3. The compound of the formula
 4. The compound of the formula
 5. The compound of the formula
 6. The compound of the formula 